Neutral ceramidase as an integral modulator for the generation of S1P and S1P-mediated signaling

Makoto Ito, Motohiro Tani, Yukihiro Yoshimura

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Citations (Scopus)

Abstract

Neutral ceramidases (CDases) are widely distributed from bacteria to humans. Enzymes from bacteria and drosophila are exclusively secretory while those in zebrafish and mammals are typical type II integral membrane proteins that occasionally detach from cells after their NH2-terminal anchor is processed. We found that the difference in enzymatic localization is entirely due to the presence of a mucin-like domain located downstream of the NH 2-terminal signal/anchor sequence of vertebrate enzymes. This sequence is not found in enzymes from bacteria and invertebrates. Overexpression of mouse neutral CDase on either the cell-surface or in the extracellular milieu significantly increased the intracellular concentration of sphingosine. Sphingosine 1-phosphate (S1P) also increased when the amount of cell-surface ceramide increased following cell treatment with bacterial sphingomyelinase. Increases were not seen in the ER. In contrast, knockdown of CDase reduced the amounts of these sphingolipid metabolites. Hence, this enzyme seems to participate in vascular S1P production where cell- and lipoprotein-bound sphingomyelin are likely to be a source of ceramide. Knockdown of neutral CDase also impaired S1P-mediated angiogenesis and heart development during zebrafish embryogenesis thereby impairing blood circulation. The CDase enzyme participates in ceramide metabolism at plasma membranes and in the extracellular milieu to regulate S1P generation and S1P-mediated signaling through the production of sphingosine.

Original languageEnglish
Title of host publicationSphingolipid Biology
PublisherSpringer Japan
Pages183-196
Number of pages14
ISBN (Print)4431341986, 9784431341987
DOIs
Publication statusPublished - 2006

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Neutral Ceramidase
Modulators
Ceramides
Enzymes
Bacteria
Sphingosine
Zebrafish
Anchors
Sphingomyelin Phosphodiesterase
Sphingolipids
Mammals
Sphingomyelins
Blood Circulation
Hemodynamics
Mucins
Invertebrates
Cell membranes
Metabolites
Protein Sorting Signals
Metabolism

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Neutral ceramidase as an integral modulator for the generation of S1P and S1P-mediated signaling. / Ito, Makoto; Tani, Motohiro; Yoshimura, Yukihiro.

Sphingolipid Biology. Springer Japan, 2006. p. 183-196.

Research output: Chapter in Book/Report/Conference proceedingChapter

Ito, Makoto ; Tani, Motohiro ; Yoshimura, Yukihiro. / Neutral ceramidase as an integral modulator for the generation of S1P and S1P-mediated signaling. Sphingolipid Biology. Springer Japan, 2006. pp. 183-196
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